20-3671968-C-G

Variant names:

• chr20-3671968-C-G
• NM_025220.5:c.1615G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025220.5(ADAM33):​c.1615G>C​(p.Glu539Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000713 in 1,403,368 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ADAM33 NM_025220.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.74

Genes affected

ADAM33 (HGNC:15478): (ADAM metallopeptidase domain 33) This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins, and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. This protein is a type I transmembrane protein implicated in asthma and bronchial hyperresponsiveness. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26258618).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM33	NM_025220.5	c.1615G>C	p.Glu539Gln	missense_variant	Exon 15 of 22	ENST00000356518.7	NP_079496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM33	ENST00000356518.7	c.1615G>C	p.Glu539Gln	missense_variant	Exon 15 of 22	1	NM_025220.5	ENSP00000348912.3
ADAM33	ENST00000379861.8	c.1615G>C	p.Glu539Gln	missense_variant	Exon 15 of 22	1		ENSP00000369190.4
ADAM33	ENST00000466620.5	n.1254G>C		non_coding_transcript_exon_variant	Exon 5 of 11	1
ADAM33	ENST00000350009.6	c.1615G>C	p.Glu539Gln	missense_variant	Exon 15 of 21	5		ENSP00000322550.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.13e-7 AC: 1 AN: 1403368 Hom.: 0 Cov.: 35 AF XY: 0.00000144 AC XY: 1 AN XY: 692620

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.25e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.069	T;.;T;.
Eigen	Benign	0.16
Eigen_PC	Benign	0.059
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.66	T;T;T;T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.26	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	L;.;.;L
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.8	N;N;.;N
REVEL	Benign	0.10
Sift	Benign	0.10	T;T;.;T
Sift4G	Benign	0.15	T;T;T;T
Polyphen		0.99	D;D;.;D
Vest4		0.23
MutPred		0.54		Loss of glycosylation at P538 (P = 0.1368);Loss of glycosylation at P538 (P = 0.1368);.;Loss of glycosylation at P538 (P = 0.1368);
MVP		0.62
MPC		0.35
ClinPred		0.90	D
GERP RS		4.3
Varity_R		0.31
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-3652615;